title: Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation.
abstract: Previous reports have shown that osteoblasts are mechano-sensitive. Low-intensity pulsed ultrasound (LIPUS) induces osteoblast differentiation and is an established therapy for bone fracture. Here we have examined how LIPUS affects inflammatory responses of osteoblasts to LPS. LPS rapidly induced mRNA expression of several chemokines including CCL2, CXCL1, and CXCL10 in both mouse osteoblast cell line and calvaria-derived osteoblasts. Simultaneous treatment by LIPUS significantly inhibited mRNA induction of CXCL1 and CXCL10 by LPS. LPS-induced phosphorylation of ERKs, p38 kinases, MEK1/2, MKK3/6, IKKs, TBK1, and Akt was decreased in LIPUS-treated osteoblasts. Furthermore, LIPUS inhibited the transcriptional activation of NF-κB responsive element and Interferon-sensitive response element (ISRE) by LPS. In a transient transfection experiment, LIPUS significantly inhibited TLR4-MyD88 complex formation. Thus LIPUS exerts anti-inflammatory effects on LPS-stimulated osteoblasts by inhibiting TLR4 signal transduction.
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Juna
authors.initials: J
authors.lastname: Nakao
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Joji
authors.initials: J
authors.lastname: Kusuyama
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Bandow
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kakimoto
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D014464:Ultrasonic Therapy; D014465:Ultrasonics
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D053245:RANK Ligand; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4
keywords: Chemokines; Lipopolysaccharide (LPS); Mechanotransduction; Osteoblasts; Toll-like receptors (TLR)